Water → HCID 71523162, compound

HRID 2178529Notes

Reaction equation

HRID 2178529 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH:18]([C:21]2[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=2[C:23]([OH:25])=O)[CH2:17]1.Cl.O[NH:32][C:33](=[NH:35])[CH3:34].ClCCl.O>CN(C=O)C>[CH3:34][C:33]1[N:35]=[C:23]([C:22]2[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=2[CH:18]2[CH2:19][CH2:20][N:16]([CH2:15][CH2:14][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[N:3]3[CH2:4][CH2:5][CH2:6][CH2:7][C:2]3=[O:1])[CH2:17]2)[O:25][N:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 89500788HCID 89500788, compoundHCID 178465668HCID 178465668, compound2×

Product 1

HCID 71523162HCID 71523162, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzoic acid a6-6 (0.31 g, 0.79 mmol, 1 eq) is dissolved in DMF and N,N′-carbonyldiimidazole (140 mg, 0.87 mmol, 1.1 eq) is added. The mixture is stirred at room temperature for 30 min, N-hydroxyacetamidine hydrochloride (95 mg, 0.87 mmol, 1.1 eq) is added and stirring is pursued for 4 hours. Another 1.1 eq of N,N′-carbonyldiimidazole and 1.1 eq of N-hydroxyacetamidine hydrochloride are added and the reaction mixture is stirred at reflux overnight. Dichloromethane and water are added and the organic layer is subsequently washed with water, HCl 1N, aqueous saturated NaHCO3 and brine. The organic layer is dried over MgSO4, evaporated and purified by preparative basic LC/MS (gradient: H2O/acetonitrile/NH4HCO3 0.5% w/v from 85/5/10 to 5/95/0 in 6.5 minutes) to afford 19 mg of 1-[2-(2-{3-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one 11.

Workup

  1. stirringstirring
  2. waitis pursued for 4 hours
  3. stirringthe reaction mixture is stirred
  4. temperatureat reflux overnight
  5. washthe organic layer is subsequently washed with water, HCl 1N, aqueous saturated NaHCO3 and brine
  6. dry with materialThe organic layer is dried over MgSO4
  7. customevaporated
  8. custompurified by preparative basic LC/MS (gradient: H2O/acetonitrile/NH4HCO3 0.5% w/v from 85/5/10 to 5/95/0 in 6.5 minutes)

Sources & evidence

ORD record
ord-ca1ac3b517f8471ea6fe630566a263ec
Source dataset
uspto-grants-2015_06
Patent number
US09067930B2

Reaction notes

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